title: Importance of mitochondrial dysfunction in oxidative stress response: A comparative study of gene expression profiles.
abstract: Mitochondria are considered to play an important role in oxidative stress response since they are a source of reactive oxygen species and are also targeted by these species. This study examined the mitochondrial conditions in cells of epithelial origin that were exposed to H(2)O(2) and found a decline in the membrane potential along with a specific loss of UQCRC1, a sub-unit of complex III, suggesting that mitochondrial dysfunction occurs upon exposure to oxidative stress. This observation led to the hypothesis that certain cellular responses to oxidative stress occurred because of mitochondrial dysfunction. When mitochondria-less (pseudo ρ0) cells were examined as a model of mitochondrial dysfunction, striking similarities were found in their cellular responses compared with those found in cells exposed to oxidative stress, including changes in gene expression and gelatinolytic enzyme activities, thus suggesting that cellular responses to oxidative stress were partly mediated by mitochondrial dysfunction. This possibility was further validated by microarray analysis, which suggested that almost one-fourth of the cellular responses to oxidative stress were mediated by mitochondrial dysfunction that accompanies oxidative stress, thereby warranting a therapeutic strategy that targets mitochondria for the treatment of oxidative stress-associated diseases.
authors.affiliation: Department of Cancer Cell Biology, Showa University School of Pharmacy, Shinagawa-ku Tokyo 142-8555, Japan. smotoko@pharm.showa-u.ac.jp
authors.forename: Motoko
authors.initials: M
authors.lastname: Shibanuma
authors.forename: Anna
authors.initials: A
authors.lastname: Inoue
authors.forename: Kyota
authors.initials: K
authors.lastname: Ushida
authors.forename: Tetsu
authors.initials: T
authors.lastname: Uchida
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Mori
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nose
mesh_terms: D000818:Animals; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000502:physiology*; D009245:NADH Dehydrogenase / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D000091402:Prohibitins; D012097:Repressor Proteins / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000091402:Prohibitins; D012097:Repressor Proteins; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D020782:Matrix Metalloproteinases; D014450:Electron Transport Complex III